ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2018
Stable Isotope Labeling Reveals Novel Insights Into Ubiquitin-Mediated Protein Aggregation With Age, Calorie Restriction, and Rapamycin Treatment.
Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Ubiquitin-specific peptidase-19 links TDP-43 aggregation to ER stress.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Nitric oxide required for transition to slower hepatic protein synthesis rates during long-term caloric restriction.The Journal of clinical investigation · 2026Article
- Ubiquitylomics: An Emerging Approach for Profiling Protein Ubiquitylation in Skeletal Muscle.Journal of cachexia, sarcopenia and muscle · 2024Review
- The transcription regulator ATF4 is a mediator of skeletal muscle aging.GeroScience · 2023Article
- TurnoveR: A Skyline External Tool for Analysis of Protein Turnover in Metabolic Labeling Studies.Journal of proteome research · 2023Article
- Determining and interpreting protein lifetimes in mammalian tissues.Trends in biochemical sciences · 2023Review
- Degradation of ribosomal and chaperone proteins is attenuated during the differentiation of replicatively aged C2C12 myoblasts.Journal of cachexia, sarcopenia and muscle · 2022Article
- Protein lifetimes in aged brains reveal a proteostatic adaptation linking physiological aging to neurodegeneration.Science advances · 2022Article
- Measurement of Protein Turnover Rates in Senescent and Non-Dividing Cultured Cells with Metabolic Labeling and Mass Spectrometry.Journal of visualized experiments : JoVE · 2022Article
- Using stable isotope labeling to advance our understanding of Alzheimer's disease etiology and pathology.Journal of neurochemistry · 2021Review
- Proximity labeling and other novel mass spectrometric approaches for spatiotemporal protein dynamics.Expert review of proteomics · 2021Review
- NADCell reports · 2021Article
- Interspecies Differences in Proteome Turnover Kinetics Are Correlated With Life Spans and Energetic Demands.Molecular & cellular proteomics : MCP · 2021Review
- Accumulation of "Old Proteins" and the Critical Need for MS-based Protein Turnover Measurements in Aging and Longevity.Proteomics · 2020Review
- Article
- Protein Turnover in Aging and Longevity.Proteomics · 2018Review
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Abstract
Accumulation of protein aggregates with age was first described in aged human tissue over 150 years ago and has since been described in virtually every human tissue. Ubiquitin modifications are a canonical marker of insoluble protein aggregates; however, the composition of most age-related inclusions remains relatively unknown. To examine the landscape of age-related protein aggregation in vivo, we performed an antibody-based pulldown of ubiquitinated proteins coupled with metabolic labeling and mass spectrometry on young and old mice on calorie restriction (CR), rapamycin (RP)-supplemented, and control diets. We show increased abundance of many ubiquitinated proteins in old mice and greater retention of preexisting (unlabeled) ubiquitinated proteins relative to their unmodified counterparts-fitting the expected profile of age-increased accumulation of long-lived aggregating proteins. Both CR and RP profoundly affected ubiquitinome composition, half-live, and the insolubility of proteins, consistent with their ability to mobilize these age-associated accumulations. Finally, confocal microscopy confirmed the aggregation of two of the top predicted aggregating proteins, keratins 8/18 and catalase, as well as their attenuation by CR and RP. Stable-isotope labeling is a powerful tool to gain novel insights into proteostasis mechanisms, including protein aggregation, and could be used to identify novel therapeutic targets in aging and protein aggregation diseases.
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